The present invention relates to novel hydrocolloid adhesive masses with increased absorption in the first few hours of use.
The invention further relates to the use of these novel hydrocolloid adhesive masses for medical purposes in dermatology or cosmetology, particularly for the production of dressings for the treatment of blisters, exudative wounds, burns and superficial, deep, chronic or acute dermo-epidermal lesions.
The treatment of superficial, deep, chronic or acute dermo-epidermal lesions, burns and, in particular, exudative wounds is a complex problem to which the dressings developed: in recent years have not provided totally satisfactory solutions.
The loss of substances caused by a mechanical compression which creates tissue ischemia, or by problems of vascular origin (irrigation, pressure, etc.), an injury (ablation of tissue,: flesh, etc.), an abscess or a burn, is generally referred to as the exudation of a wound. The phenomenon of exudation corresponds to excretion of the biological fluids produced by the wound throughout the healing process.
Exudation originates from the blood and is controlled by the mediators of the inflammatory reaction (vasodilation and vasoconstriction) with passage of these fluids through the vascular membranes. These fluids then flood the bed of the wound and constitute the factors which favor degradation of the perilesional healthy tissues, accompanied in particular by maceration phenomena and risks of superinfection.
The role of a dressing is to absorb these fluids while at the same time maintaining in contact with the wound a moist environment which favors the healing processes.
The ideal dressing must therefore be capable of absorbing these exudates throughout the healing of the wound.
Depending on the severity of the wound, this. healing process may extend from a few days, for wounds producing very little exudation, to several months. This involves changing the dressing frequently in order to maintain its absorption capacity and its efficacy.
To minimize the number of changes of dressing, which are traumatizing for the patient and for the healing quality (pulling-away of neoformed tissues, bleeding, pain, etc.), so-called xe2x80x9chydrocolloidxe2x80x9d dressings based on hydrocolloid adhesive masses are now used to maintain an absorption capacity over 2 to 4 days.
These hydrocolloid adhesive masses, also described as hydrophilic adhesive masses, are formed mainly of an adhesive matrix, generally consisting of at least one elastomer selected from polymers such as polyisobutylenes or poly(styrene/olefin/styrene) block copolymers, which may or may not be associated with adhesion improvers such as sticky resins, or tackifying resins, plasticizers such as polybutenes or plasticizing oils, or cohesion improvers such as butyl rubbers, etc., and of one or more hydrocolloids.
Numerous hydrocolloid adhesive masses employed in the production of such dressings have already been described. Examples which may thus be mentioned are patent US:3 972 328 and the following patent applications: FR-A-2 495 473, EP-A-130 061 and EP-A-302 536.
However, none of these documents tackles another important aspect of exudation, namely its kinetic aspect over time.
It is in fact known that the phenomenon of exudation is always more important at the start of the healing process, which corresponds to the critical phase of the inflammatory reaction. This inflammatory reaction is most important during the first 4 hours, so it is a matter of urgency to re-establish the hemostatic equilibrium of the wound, i.e. to increase the absorption capacity during the first few hours. In fact, the more rapidly this equilibrium is reached, the less the wound will weep and the better the absorption capacity of the dressing will be maintained at a high level over several days. It will thus be possible to make the changes of dressing less frequent and avoid the associated disadvantages already mentioned.
Likewise, each time the dressing is changed when the wound is tended, cleaned and disinfected, and before a new dressing is applied, the wound is faced with a more aggressive environment (contact with the air, loss of moisture, etc.). This causes a resumption of the inflammatory reaction, which will induce an increase in the exudates produced, so there is again a need in this case to increase the absorption capacity during the first few hours.
An ideal dressing should therefore be adapted to the amount of exudates produced, but also to theirate of production.
To adapt the absorption capacity to the rate of production, one might consider increasing the amount of hydrocolloid which gives these adhesive masses their absorption property. However, if too much of this type of product is incorporated into the adhesive mass, said products will swell proportionately to their concentration and will degrade the physical properties of the dressing, resulting in a loss of cohesion and meaning that the dressing falls apart when removed or may even be wasted. Consequently, this solution cannot be satisfactory because this situation once again raises the problems associated with changing of the dressing and with the life of the dressing.
Under these conditions, the object of the present invention is to solve the new technical problem consisting in the provision of a hydrocolloid adhesive mass of novel composition which has a high absorption as from the first few hours without impairment of its properties of cohesion, adhesion and manageability in the medium and long term.
It has been discovered that it is possible to solve this technical problem in an entirely satisfactory manner, which is simple to implement, by incorporating an ethoxylated sorbitan fatty acid ester, preferably a monoester, into a traditional hydrocolloid adhesive mass. It is this discovery which constitutes the basis of the present invention.
Furthermore, it has been found that the addition of an ethoxylated sorbitan fatty acid ester to a traditional hydrocolloid adhesive mass, particularly an adhesive mass comprising an elastomer of the poly(styrene/isoprene/styrene) type, affords a significant increase in the capacity of said mass to discharge the absorbed fluids by increasing the permeability to water vapor. Thus the novel hydrocolloid masses according to the invention can be used to produce dressings which are capable of eliminating the absorbed fluids and, consequently, of maintaining an absorption-elimination equilibrium and a moist environment favorable to healing.
Thus, according to a first feature, the present invention relates in general terms to a hydrocolloid adhesive mass consisting of a hydrocolloid and an adhesive matrix, with which an acrylate polymer with a glass transition temperature below xe2x88x9220xc2x0 C. may or may not be associated, and of an ethoxylated fatty acid ester.
More precisely, the present invention relates to a hydrocolloid adhesive mass useful especially for medical purposes, characterized in that said hydrocolloid adhesive mass comprises:
(a) 0.2 to 5 parts by weight of an ethoxylated sorbitan fatty acid ester;
(b) 20 to 50 parts by weight of a hydrocolloid;
(c) 32 to 120 parts by weight of an adhesive matrix made up of one or more polymers selected from poly(styrene/olefin/styrene) block copolymers, low-molecular polyisobutylenes and high-molecular polyisobutylenes, and one or more compounds selected from sticky resins, or tackifying resins, plasticizers, polybutenes, antioxidants, ethylene/vinyl acetate copolymers, butyl rubbers and ethylene/propylene block copolymers; and
(d) 0 to 15 parts by weight of an acrylate polymer with a glass transition temperature below xe2x88x9220xc2x0 C.
Ethoxylated sorbitan fatty acid ester is understood here as denoting ethoxylated sorbitan fatty acid esters (especially monoesters, triesters or mixtures thereof) in which each fatty acid part of the ester contains from 8 to 22 carbon atoms and is a linear or branched chain, preferably a linear chain, which is saturated or possesses one or more sites of olefinic unsaturation.
Within the framework of the present invention, particularly preferred ethoxylated sorbitan fatty acid esters will be those referred to as polysorbates and corresponding to the ethoxylated sorbitan fatty acid monoesters and triesters respectively represented by formulae I and II below, in which the sum w+x+y+z can take the value 20, 5 or 4 and R is the hydrocarbon part of the fatty acid containing from 7 to 21 carbon atoms. 
Thus preferred ethoxylated sorbitan monoesters of formula I will be those for which the sum w+x+y+z=20, for example ethoxylated sorbitan monolaurate (also called polysorbate 20), ethoxylated sorbitan monopalmitate (also called polysorbate 40), ethoxylated sorbitan monostearate (also called polysorbate 60), ethoxylated sorbitan monooleate (also called polysorbate 80) and ethoxylated sorbitan monoisostearate (also called polysorbate 120). Preferred monoesters of formula I for which w+x+y+z=4 will be ethoxylated sorbitan monolaurate (also called polysorbate 21) and ethoxylated sorbitan monostearate (also called polysorbate 61). Finally, the preferred monoester of formula I for which w+x+y+z=5 will be ethoxylated sorbitan monooleate (also called polysorbate 81).
Likewise, preferred ethoxylated sorbitan triesters of formula II will be those for which the sum w+x+y+z=20, for example ethoxylated sorbitan tristearate (also called polysorbate 65) and ethoxylated sorbitan trioleate (also called polysorbate 85).
Within the framework of the present invention, polysorbate 80 will be very particularly preferred, examples being the products marketed by SEPPIC under the names MONTANOX(copyright) 80 and MONTANOX(copyright) 80VG (which has an identical composition to the first product except that in this case the fatty acid part is of vegetable origin).
According to a second feature, the present invention relates to the use of these hydrocolloid adhesive masses for the production of dressings especially for the treatment of blisters, superficial, deep, chronic or acute dermo-epidermal lesions, exudative wounds and bums.
The adhesive matrices which can be used in the production of the hydrocolloid adhesive masses are the ones commonly employed by those skilled in the art. They are formed of at least one elastomer selected from polymers such as polyisobutylenes or poly(styrene/olefin/styrene) block copolymers, for example poly(styrene/isoprene/styrene), poly(styrene/butadiene/styrene) or poly(styrene/ethylene/butylene/styrene), which may or may not be associated with antioxidants, adhesion improvers such as sticky resins, or xe2x80x9ctackifyingxe2x80x9d resins, plasticizers such as polybutenes or plasticizing oils, or cohesion improvers such as butyl rubbers, etc.
Such compositions are thus defined in chapter 7, xe2x80x9cWound Dressingsxe2x80x9d, pages 158 to 171, of xe2x80x9cAdvances in Pressure Sensitive Adhesive Technology-2xe2x80x9d, published in April 95 by Donatas Satas.
Reference may also be made in this respect to the prior art documents mentioned above for the definitions of all the compounds used in these formulations and their respective proportions in the adhesive matrix.
Thus, in the case of an adhesive matrix based on polyisobutylene elastomer, polyisobutylenes with a low molecular weight of the order of 40,000 to 80,000 daltons will be used, such as the compounds marketed under the name VISTANEX(copyright) by EXXON CHEMICAL or under the name OPPANOL(copyright) by BASF.
The products marketed under the names VISTANEX(copyright) LM-MS, VISTANEX(copyright) LM-MH, OPPANOL(copyright) B12 and OPPANOL(copyright) B15 will be particularly preferred.
The latter products may be used by themselves or in a mixture.
If necessary, these polyisobutylenes may be associated with additional compounds for improving the properties of elasticity, strength or cohesion, such as polyisobutylenes with a high molecular weight of the order of 400,000 to 2,000,000 daltons, for example the: products marketed by EXXON CHEMICAL under the names VISTANEX(copyright) L-80 or VISTANEX(copyright) L- 100, ethylene/vinyl acetate copolymers, for example those marketed under the name ELVAX(copyright) by DUPONT or under the names ULTRATHENE(copyright) and VYNATHENE(copyright) by U.S.I. Chemicals, ethylene/propylene block copolymers, for example those marketed by DUPONT under the name NORDEL(copyright), or butyl rubbers, for example those marketed under the names GRADE(copyright) 065 or GRADE(copyright) 067 by EXXON CHEMICAL.
Plasticizers such as polybutenes, for example those marketed by BP CHEMICALS under the. name NAPVIS(copyright) 10, can also be incorporated into these adhesive matrices.
Such adhesive matrices will be formulated in conventional manner by those skilled in the art to give the desired adhesive and mechanical properties by adapting the amount of each compound.
Block copolymers of the poly(styrene/olefin/styrene) type may likewise be added to these adhesive matrices based on polyisobutylenes. In that case it will be preferable to use poly(styrene/isoprene/styrene) copolymers, for example the products marketed under the names KRATON(copyright) D-1107 or KRATON(copyright) 1161 by SHELL CHEMICALS or the product marketed under the name VECTOR(copyright) 4113 by EXXON CHEMICAL, or poly(styrene/butadiene/styrene) copolymers, for example the product marketed under the name KRATON(copyright) D-1102 by SHELL CHEMICALS.
Such formulations of adhesive matrices are described for example in patent application EP-A-130 061.
Similarly, it will be possible to use adhesive matrices based solely on an elastomer of the poly(styrene/olefin/styrene) block copolymer type, particularly those based on poly(styrene/isoprene/styrene) or poly(styrene/ethyleneibutylene/styrene), which are associated with plasticizers, xe2x80x9ctackifyingxe2x80x9d resins, antioxidants, etc. to give the desired adhesive and cohesive properties.
Such formulations of adhesive matrices are also perfectly familiar to those skilled in the art.
The block copolymers of the styrene/olefin/styrene type which can be used within the framework of the preparation of these adhesive matrices are the ones normally used by those skilled in the art, and reference may be made in this respect to the prior art document mentioned above.
The olefin blocks of these copolymers can consist of isoprene, butadiene, ethylene/butylene or ethylene/propylene units and mixtures thereof.
Within the framework of the present invention, poly(styrene/isoprene/styrene) three-block copolymers are preferred.
Three-block copolymer of the poly(styrene/isoprene/styrene) type [abbreviated to poly(SIS)] is understood here as meaning a poly(SIS) material with a styrene content of between 14 and 52% by weight, based on the weight of said poly(SIS). This expression also covers poly(SIS) materials containing a mixture of poly(SIS) three-block copolymers and two-block copolymers of the poly(styrene/isoprene) type.
Such products, which are well known to those skilled in the art, are marketed for example by SHELL and EXXON CHEMICAL under the names KRATON(copyright) D and VECTOR(copyright) respectively.
Within the framework of the present invention, three-block copolymers with a styrene content of between 14 and 30% by weight, based on the weight of said poly(SIS), are preferred. The products marketed by EXXON CHEMICAL and SHELL CHEMICALS under the respective names VECTOR(copyright) 4114 and KRATON(copyright) D-1111CS will be particularly preferred.
Among the tackifying resins suitable for the production of these adhesive matrices, there may be mentioned the resins generally employed in the field of adhesives by those skilled in the art, such as modified polyterpene or terpene resins, hydrogenated rosin resins, polymerized rosin resins, rosin ester resins, hydrocarbon resins, mixtures of aromatic and aliphatic resins, etc. A synthetic resin formed of C5/C9 copolymers and marketed by GOOD YEAR under the name WINGTACK(copyright) 86 will be particularly preferred within the framework of the present invention.
Antioxidants are understood here as denoting the compounds commonly employed by those skilled in the art for ensuring that the compounds used in the formulation of the matrices, particularly the tackifying resins and the block copolymers, are stable towards oxygen, heat, ozone and ultraviolet radiation. It is possible to use one or more of these antioxidants in association.
Appropriate antioxidants which may be mentioned are phenolic antioxidants, for example the products marketed by CIBA-GEIGY under the names IRGANOX(copyright) 1010, IRGANOX(copyright) 565 and IRGANOX(copyright) 1076, and sulfur-containing antioxidants, for example the zinc dibutyldithiocarbamate marketed by AKZO under the name PERKACIT(copyright) ZDBC.
The association of IRGANOX(copyright) 1010 and PERKACIT(copyright) ZDBC will be preferred within the framework of the present invention.
Any type of plasticizer normally used by those skilled in the art for the preparation of an adhesive matrix based on styrene/olefin/styrene block copolymer can be used within the framework of the present invention, although it will be preferable to use plasticizing oils.
Plasticizing oils are understood here as denoting the mineral or vegetable oils commonly employed by those skilled in the art for plasticizing the block copolymers of the styrene/olefin/styrene type used in the composition of the adhesive matrices employed in hydrocolloid adhesive masses.
The mineral oils generally used are mixtures of compounds of a paraffinic, naphthenic or aromatic nature in variable proportions.
Examples of plasticizing oils which may thus be mentioned are the products marketed by SHELL under the names ONDINA(copyright) and RISELLA(copyright) in the case of mixtures based on naphthenic and paraffinic compounds, or under the name CATENEX(copyright) in the case of mixtures based on naphthenic, aromatic and paraffinic compounds.
The mineral plasticizing oil marketed under the name ONDINA(copyright) 68 will be particularly preferred within the framework of the present invention.
Within the framework of the production of the hydrocolloid adhesive masses according to the invention, hydrocolloids are understood here as meaning the compounds commonly used by those skilled in the art which are known for their ability to absorb hydrophilic liquids, particularly water, and transport them rapidly. Examples of appropriate hydrocolloids which may be mentioned are polyvinyl alcohol, gelatin, pectin, sodium alginates, natural vegetable gums such as carob gum, karaya gum, guar gum, gum arabic, etc., and cellulose derivatives such as hydroxyethyl celluloses, hydroxypropyl celluloses, carboxymethyl celluloses and their alkali metal salts such as the sodium or calcium salts. These hydrocolloids may be used by themselves or in association.
The alkali metal salts of carboxymethyl cellulose, particularly sodium carboxymethyl cellulose, will be preferred within the framework of the present invention.
In one currently preferred embodiment, the hydrocolloid adhesive mass also contains an acrylate polymer with a glass transition temperature (Tg) below xe2x88x9220xc2x0 C.
Such acrylate compounds are copolymers formed of:
either at least one monomer selected from the group consisting of acrylic acid alkyl esters in which the linear or branched alkyl group of the ester contains 1 to 18 carbon atoms, preferably 4 to 10 carbon atoms and particularly 4 to 8 carbon atoms, for example methyl, ethyl, n-propyl, n-butyl, isobutyl, n-hexyl, 2-ethylhexyl, n-octyl, isooctyl, n-decyl and n-dodecyl acrylates, associated with acrylic acid;
or at least one monomer selected from the group consisting of acrylic acid alkyl esters in which the linear or branched alkyl group of the ester contains 1 to 18 carbon atoms, preferably 4 to 10 carbon atoms and particularly 4 to 8 carbon atoms, for example methyl, ethyl, n-propyl, n-butyl, isobutyl, n-hexyl, 2-ethylhexyl, n-octyl, isooctyl, n-decyl and n-dodecyl acrylates.
The respective percentages or proportions of these different monomers are adjusted to give a copolymer with the desired glass transition temperature, i.e. below xe2x88x9220xc2x0 C.
A copolymer containing at least one monomer selected from n-butyl acrylate, 2-ethylhexyl acrylate and isooctyl acrylate, copolymerized with acrylic acid, will preferably be used within the framework of the present invention.
Copolymers containing from 1 to 20% and preferably 1 to 10% by weight of acrylic acid, expressed relative to the total weight of all the monomers, will be very particularly preferred.
Such acrylate compounds can also be homopolymers whose constituent monomer is selected from the group consisting of acrylic acid alkyl esters in which the alkyl group of the ester is either a linear alkyl group containing 2 to 12 carbon atoms or an isobutyl, 2-ethylhexyl or isooctyl group.
Among these homopolymers, poly-n-butyl acrylate will be preferred within the framework of the present invention.
According to one particular characteristic of the invention, the products well known to those skilled in the art for their use in a solventless coating process, known as a hot melt process, will be chosen.
Examples which may thus be mentioned are the products marketed by BASF under the following names:
ACRONAL(copyright) A150F (n-butyl acrylate homopolymer with a glass transition temperature of xe2x88x9241xc2x0 C.),
ACRONAL(copyright) DS3429 (n-butyl acrylate/2-ethylhexyl acrylate/acrylic acid copolymer with a glass transition temperature of xe2x88x9231xc2x0 C.), and
ACRONAL(copyright) DS3458 (n-butyl acrylate/acrylic acid copolymer with a glass transition temperature of xe2x88x9239xc2x0 C.).
The product marketed by MONSANTO under the name MODAFLOW(copyright) (ethyl acrylate/2-ethylhexyl acrylate copolymer) may also be mentioned.
The acrylate polymer marketed under the name ACRONAL(copyright) DS3458 will be very particularly preferred within the framework of the present invention.
In one particularly preferred embodiment of the present invention, for adhesive matrices based solely on poly(styrene/olefin/styrene) block copolymers, a hydrocolloid adhesive mass is recommended which comprises:
a) 10 to 35 parts by weight of a poly(styrene/isoprene/styrene) three-block copolymer;
b) 20 to 50 parts by weight of a tackifying resin;
c) 0.5 to 15 parts by weight of an acrylate polymer with a glass transition temperature below xe2x88x9220xc2x0 C.;
d) 2 to 25 parts by weight of a plasticizing oil;
e) 20 to 50 parts by weight of a hydrocolloid;
f) 0.1 to 2 parts by weight of at least one antioxidant; and
g) 0.2 to 5 parts by weight of ethoxylated sorbitan monooleate.
In another preferred embodiment, this hydrophilic adhesive mass comprises, for a total of 100 parts by weight:
a) 18 to 22 and preferably 17.7 parts by weight of a poly(styrene/isoprene/styrene) three-block copolymer;
b) 20 to 35 and preferably 26.5 parts by weight of a tackifying resin;
c) 3 to 8 and preferably 6.5 parts by weight of an n-butyl acrylate/acrylic acid copolymer with a glass, transition temperature of xe2x88x9239xc2x0 C.;
d) 10 to 20 and preferably 12.4 parts by weight of a mineral plasticizing oil;
e) 25 to 40 and preferably 35.7 parts by weight of sodium carboxymethyl cellulose;
f) 0.3 to 0.8 and preferably 0.75 part by weight of a phenolic antioxidant and 0.3 to 0.8 and preferably 0.35 part by weight of the sulfur-containing antioxidant zinc dibutyldithiocarbamate; and
g) 0.2 to 3 and preferably 0.5 part by weight of polysorbate 80.
Likewise, in one particularly preferred embodiment of the invention, for adhesive matrices based on polyisobutylene, a hydrocolloid adhesive mass is recommended which comprises:
a) 5 to 20 parts by weight of a (styrene/isoprene/styrene) copolymer;
b) 25 to 50 parts by weight of a low-molecular polyisobutylene;
c) 2 to 20 parts by weight of a polybutene;
d) 20 to 50 parts by weight of a hydrocolloid;
e) 0.2 to 5 parts by weight of an ethoxylated sorbitan monooleate;
f) 0.5 to 15 parts by weight of an acrylate polymer with a glass transition temperature below xe2x88x9220xc2x0 C.; and
g) 0.1 to 2 parts by weight of at least one antioxidant.
The hydrocolloid adhesive mass according to the invention is useful for medical purposes in any application in which it is necessary to absorb fluids or liquids as from the first few hours. Thus there may be mentioned the production of dressings and bandages for the treatment of blisters, superficial, deep, chronic or acute dermo-epidermal lesions, exudative wounds and burns, and the production of adhesive joints employed in ostomy.
Within the framework of these applications, various products of a dermatological, cosmetological or therapeutic nature can be added to the formulation of the hydrocolloid adhesive mass, examples being antifungals, antimicrobials or antibacterials such as sulfadiazine silver, pH regulators, healing accelerators, vitamins, plant extracts, trace elements, local anesthetics, odor traps, menthol, methyl salicylate, hormones, antiinflammatories, etc.
Within the framework of the production of a dressing for the treatment of blisters or the treatment or protection of wounds, different categories of dermo-epidermal lesions, burns and bedsores, the hydrocolloid adhesive mass according to the invention is coated onto an appropriate support in the desired weight per unit area, according to the techniques known to those skilled in the art, by means of a solvent phase process or, preferably, by means of a hot melt process, or solventless process, at a temperature of between 110 and 160xc2x0 C.
The support is chosen as a function of the properties required (leaktightness, elasticity, etc.), depending on the type of dressing and the intended application.
It can take the form of a film with a thickness varying from 5 to 150 xcexcm, or a nonwoven or a foam with a thickness of 10 to 500 xcexcm. These supports based on synthetic or natural materials are the ones generally used by those skilled in the art in the field of dressings and the above-mentioned medical applications.
Thus there may be mentioned foams made of polyethylene, polyurethane or PVC, and nonwovens made of polypropylene, polyamide, polyester, ethyl cellulose, etc. It will be preferable, however, to use films as supports, especially polyurethane films, low density polyethylene films, for example those marketed by SOPAL, films based on thermoplastic polyether/polyester copolymer, for example the products marketed under the trade mark Hytrel(copyright) by DUPONT DE NEMOURS, or composites based on polyurethane and a nonwoven.
Polyurethane films such as the products marketed by Smith and Nephew under the reference LASSO, or polyurethane films produced from the polyurethane marketed under the name UCECOAT(copyright) by UCB or under the name ESTANE(copyright) by B.F. GOODRICH, will be preferred within the framework of the present invention.
The dressings produced from the hydrocolloid adhesive mass according to the invention can have any geometric shape, i.e. square, rectangular, circular or oval. Likewise, they can be of any size, according to the surface area of the part to be treated or protected.
In practical terms, the surface of the adhesive mass which is not bonded to the support may be covered with a protective layer or film to be peeled off before the dressing is used. The assembly formed in this way may itself be packaged in a leaktight protection, for example made of polyethylene/aluminum composites, or in blister packs.